The Messenger Apps of the cell: Extracellular Vesicles as Regulatory Messengers of Microglial Function in the CNS
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INVITED REVIEW
The Messenger Apps of the cell: Extracellular Vesicles as Regulatory Messengers of Microglial Function in the CNS Adeyemi A. Olanrewaju 1 & Ramin M. Hakami 1 Received: 31 March 2019 / Accepted: 20 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The intense effort of investigators, in particular during the past decade, has highlighted the importance of extracellular vesicles (EVs) such as exosomes in regulating both innate and adaptive immunity in the course of a variety of infections, with clear implications for development of novel vaccines, therapeutics, and diagnostics. Current and future efforts now need to focus strongly on teasing apart the intricate and complex molecular mechanisms that operate during EV regulation of immunity. In this review, we discuss recent advances that bear on our current understanding of how EVs, including exosomes, can contribute to the innate immune functions of microglia within the central nervous system (CNS), and we also highlight future important mechanistic questions that need to be addressed. In particular, recent findings that highlight the crosstalk between autophagy and exosome pathways and their implications for innate immune functions of microglia will be presented. Microglial activation has been shown to play a key role in neuroAIDS, a neuro-infectious disease for which the importance of exosome functions, including exosome-autophagy interplay, has been reported. The importance of exosomes and exosome-autophagy crosstalk involving microglia has also been shown for the Parkinson’s disease (PD), a neurodegenerative disease that is thought to be linked with immune dysfunction and involve infectious agents as trigger. Considering the accumulation of recent findings and the vibrancy of the EV field, we anticipate that future studies will continue to have a deep impact on our understanding of the CNS pathologies that are influenced by the functions of microglia and of the infectious disease mechanisms in general. Keywords Exosome . Extracellular Vesicle . Autophagy . Microglia . CNS . Infection . Innate . Immunity . Vaccine . Therapy
Brief Introduction Extracellular vesicles (EV), including exosomes (EX), have attracted significant attention among scientists during the last decade as the influence of their communicative effects in a number of different human pathologies, including infectious diseases, have become apparent (Delorme-Axford et al. 2013). Their role in regulating immunity first became a subject of interest when it was discovered that certain cells secretes EVs harboring major histocompatibility complex class II (MHC class II), which can induce antigen specific MHC class II T cell responses (Raposo et al. 1996; Schorey and Harding 2016). Since this discovery, many studies have
* Ramin M. Hakami [email protected] 1
School of Systems Biology, and the National Center for Biodefense and Infectious Diseases, George Mason University, Manassas, VA 20110, USA
highlighted the ability of EVs to influence both innate
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